Ch. 8 Cell Cycle Control by pRb Flashcards
dna damage checkpoint S
S phase, DNA rep is halted if genome is damaged
dna damage checkpoint G1
entrance into S is blocked if genome is damaged
DNA replication not complete then…
entrance into M blocked
chromatids not properly assembled on mitotic spindle…
entrance into anaphase blocked
Rad 17
responsible for preventing re- replication of already replicated chromosomal DNA, results in increases of the ploidy of the cell
Bulb1
normally prevents the separation of chromosomes in the event that one or more
chromosomal pairs are not properly aligned;
ATR
responsible for halting further DNA replication until stalled replication forks are repaired
When are cells responsive to growth factors and TGFβ?
During G1
Cyclins associated with CDKs activate…
the catalytic activity of their CDK partners
Cells are no longer responsive to growth factors or TGFβ after passing the…
restriction point
B-type cyclins increase in
anticipation of mitosis
at the end of mitosis cyclin B levels are
dramatically decreased
D-type cyclins are controlled by
extracellular signals (mitogenic growth factors)
how does removal of growth factor affect cyclin D1
rapid decrease in D1 levels
P21Cip1, p27Kip1 inhibit
Cyclin CDKs
When TGF-β is applied to epithelial cells, it triggers downstream responses that
antagonize cell proliferation
P21Cip1 levels are increased in response to
dna damage
In low grade, less advanced human mammary carcinomas, levels of activated Akt/PKB
are low and and p27Kip1 is able to carry out its anti-proliferative function in the nucleus
In high grade tumors, activated Akt/PKB levels are
high and p27Kip1 is now found in the cytoplasm and, therefore, cannot inhibit cyclin-CDK complexes
pRb is unphosphorylated in
G0
pRb weakly phosphorylated in
G1 = growth inhibitory
If cell experiences serious physiologic stress while in S phase or G2
pRB phosphorylation can be reversed
pRB
guardian of restriction point gate
What is amplified in about 1/3 of HNSCC tumors
CD1
